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Ceravolo R.,University of Pisa | Brusa L.,UOC Neurologia | Galati S.,University of Rome Tor Vergata | Volterrani D.,University of Pisa | And 7 more authors.
European Journal of Neurology | Year: 2011

Background and purpose: To evaluate the effects of 25-Hz deep brain stimulation of the nucleus tegmenti pedunculopontini (PPTg) on brain metabolic activity. Methods: Six patients with Parkinson's disease (PD) who had bilateral stereotactic implantation of PPTg at least 12months prior to evaluation were included in our study. All underwent, in separate sessions, 18-FDG-PET in core assessment programme for intra-cerebral transplantation as well as motor evaluation [Unified Parkinson's disease rating scale (UPDRS) - section III] and a battery of cognitive testing. Results: PPTg-ON (low bipolar contacts, 25Hz) promoted a significant increase of glucose utilization in bilateral prefrontal areas including dorsolateral prefrontal cortex (DLPFC, BA9), orbito-frontal cortex (BA47), anterior cingulate (BA 25-32), superior frontal gyrus (BA 10) and supramarginal gyrus (BA40); a significant increase of uptake and consumption of FDG also occurred in the left ventral striatum, left subgyral (BA 46), right insula (BA 13) and right superior temporal gyrus (BA 22). PPTg-ON was associated with a significant decrease of glucose utilization in the left cerebellar anterior lobe (culmen) and right cerebellar posterior lobe (declive). In the same patients, PPTg-ON improved delayed recall (P<0.05) and executive functions whilst the UPDRS revealed a modest (-21%) and variable treatment effect. Conclusions: Low frequency stimulation of PPTg, a sub-region of the pedunculopontine nucleus complex, causes a minor motor benefit but a peculiar profile of cognitive improvement associated with a significant increase in FDG consumption in both prefrontal areas and mono-lateral ventral striatum. These data are consistent with multiple limbic and/or associative domains modulated by PPTg stimulation in our patients with PD. © 2010 The Author(s). European Journal of Neurology © 2010 EFNS. Source

Stefani A.,University of Rome Tor Vergata | Brusa L.,UOC Neurologia | Olivola E.,University of Rome Tor Vergata | Pierantozzi M.,University of Rome Tor Vergata | Martorana A.,University of Rome Tor Vergata
Journal of Neural Transmission | Year: 2012

Dementia has become a relevant problem associated with the elderly in our countries. Increased interest in the field has yielded a copious literature, so far mostly centered on Alzheimer's dementia. Cerebrospinal fluid (CSF) analysis combined with neuropsychology, even in absence of neuroimaging, represents the gold standard to reach a diagnosis when cortical cognitive impairment prevails. In view of this, low levels of CSF amyloid peptides β (Aβ) and high tau/Aβ protein ratio, despite prominent impairment of executive functions or concomitant vascular burden, facilitate the diagnosis of Alzheimer's disease. Conversely, an early cognitive impairment occurring in patients suffering from Parkinson's disease (PD) or Lewy body disorders (LBDs), both diagnoses posed on pure clinical grounds, remains quite elusive in term of biomarkers or neuropsychological assessment. Whether PD with dementia (PDD) and dementia with Lewy bodies (DLB) represent further steps along with a continuum of the same progressive degeneration due to Lewy bodies deposition, rather then the association of Lewy bodies and Aβ pathology, remains a challenging issue. Aim of this work is to set a state-of-the-art on the neuropsychological profiles of both or DLB. Then, we will focus on the ongoing controversies about the specificity of the standard CSF biomarkers if applied to extrapyramidal disorders. Our conclusions are that the CSF pattern, in PDD and DLB, can certainly be distinct from that in AD, though mechanisms leading to dementia could be shared among them. It is possible that, by combining imaging tracers, neuropsychologically careful assessment and renewed CSF biomarkers, DLB can be better distinguished in subgroups, depending on the presence or absence of a relevant amyloid burden. However, more complete data, possibly collected in fieri during the progressive derangement of cognitive abilities, are needed to improve our ability to decipher and treat these entities. © Springer-Verlag 2012. Source

Poletti M.,UOC Neurologia
Rivista di Psichiatria | Year: 2010

Reward processing permits to establish if and how an environmental stimulus or a future goal is reinforcing or punishing for the subject. This process is at the basis of reinforcement learning and decision making; is principally based on the orbitofrontal cortex and its connections with the striatum and the limbic system. If a dysfunctional reward processing has been often reported in substance abusers or pathologic gamblers, recent studies reported a dysfunction of this process in patients with other psychiatric disorders, previously not assessed by this experimental perspective, for example attention deficit/hyperactivity disorder, mood disorders, eating behaviour disorders and cluster B personality disorders. Experimental findings on a dysfunctional reward processing in these disorders are reviewed and discussed, in order to trace directions for future studies, that need to clarify if different dysfunctions are associated to different psychiatric disorders. Source

Ghezzi A.,Multiple Sclerosis Study Center | Moiola L.,Hospital S. Raffaele | Pozzilli C.,University of Rome La Sapienza | Brescia-Morra V.,University of Naples Federico II | And 4 more authors.
BMC Neurology | Year: 2015

Background: Natalizumab is a promising option for pediatric multiple sclerosis (MS) patients with active evolution and a poor response to Interferon-beta or Glatiramer Acetate. However, no data are available in large cohorts of patients and after a long-term follow up. Our study was planned to shed lights on this topic. Methods: A registry was established in 2007 in Italy to collect MS cases treated with Natalizumab (NA) before 18 years of age. Results: 101 patients were included (69 females), mean age of MS onset 12.9±2.7 years, mean age at NA initiation 14.7±2.4 years. Mean treatment duration was 34.2±18.3 months. During NA treatment, a total of 15 relapses were recorded in 9 patients, annualized relapse rate was 2.3±1.0 in the year prior to NA and decreased to 0.1±0.3 (p<0.001) at last NA infusion. Mean Expanded Disability Status Scale (EDSS) decreased from 2.6±1.3 at initiation of NA to 1.8±1.2 at the time of last visit (p<0.001). At brain MRI, new T2 or Gd enhancing lesions were observed in 10/91 patients after 6 months, 6/87 after 12 months, 2/61 after 18 months, 2/68 after 24 months, 3/62 after 30 months, and 5/43 at longer follow up. At the time of last observation, 58 % of patients were free from clinical (relapses/increased EDSS) and/or MRI activity (new T2 or gadolinium-enhancing lesions). No relevant adverse events were recorded. Discussion: NA was safe, well tolerated and very efficacious in the large majority of patients. Our data support the use of this medication in subjects with pediatric MS and an aggressive course. Conclusions: A relevant reduction of relapse rate and EDSS was observed during NA treatment, compared to pre-treatment period. No evidence of disease activity (NEDA) occurred in 58 % of cases. © 2015 Ghezzi et al. Source

Alessandro S.,IRCCS Fondazione S. Lucia | Alessandro S.,NeuroLogica | Ceravolo R.,University of Pisa | Brusa L.,UOC Neurologia | And 8 more authors.
Journal of the Neurological Sciences | Year: 2010

Between 2005 and 2007, six patients affected by idiopathic Parkinson's disease (IPD) were submitted to the bilateral implantation (and subsequent deep brain stimulation - DBS) of the pedunculopontine nucleus (PPN) plus the subthalamic nucleus (STN). This review synthesizes the effects of PPN low-frequency stimulation on non-motor functions, focusing on patient sleep quality and cognitive performance. If not associated to STN-DBS, PPN-DBS promoted a modest amelioration of patient motor performance. However, during PPN-DBS, they experienced on the one hand a significant improvement in executive functions and working memory, on the other hand a beneficial change in sleep architecture. Overall, the limited sample hampers definite conclusions. Yet, although the PPN-DBS induced motor effects are quite disappointing (discouraging extended trials based upon the sole PPN implantation), the neuropsychological profile supports the contention by which in selected PD patients, with subtle cognitive deficits or vanished efficacy of previous implanted STN, PPN-DBS might still represent a reliable and compassionate option. © 2009 Elsevier B.V. All rights reserved. Source

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